[Changes in biological properties of botulinum neurotoxin a induced by chemical modification of its molecule by tryptophan and tyrosine].
Using spectrophotometric titration of botulinic neurotoxin A by N-bromosuccinimide, the oxidation of one tryptophane residue was shown to induce an almost complete detoxication of the toxic protein. The conformation of the toxin molecule remained thereby unchanged, as well as the precipitation capacity of the modified toxin after oxidation of two tryptophane residues. The toxin with three or more modified tryptophane residues did not produce precipitation bands with antiserum against original toxin. Nitration of the tyrosine residues in the neurotoxin molecule with tetranitromethane gradually decreased its toxicity. All nitrous derivatives of toxin (both toxic and non-toxic ones) containing 2-18 modified tyrosine residues revealed a precipitating capacity in a reaction with antiserum against original toxin and anfragment sera. The non-toxic toxin nitrous derivatives with 15-18 modified tyrosine residues possessed partial serological affinity for original toxin in a reaction with antiserum against toxin and did not interact with antisera against toxin fragments. The conformation of molecules of toxin nitrous derivatives with 4-5 modified tyrosine residues was not changed irrespective of a 80% loss of the enzyme toxicity.
D000818:Animals; D000936:Antigen-Antibody Complex; D001665:Binding Sites; D001905:Botulinum Toxins / Q000633:toxicity; D001974:Bromosuccinimide / Q000494:pharmacology*; D007106:Immune Sera; D005779:Immunodiffusion; D007700:Kinetics; D051379:Mice; D011485:Protein Binding; D011817:Rabbits; D013388:Succinimides / Q000494:pharmacology*; D014364:Tryptophan / Q000032:analysis*; D014443:Tyrosine / Q000032:analysis*
D000936:Antigen-Antibody Complex; D007106:Immune Sera; D013388:Succinimides; D014443:Tyrosine; D014364:Tryptophan; D001905:Botulinum Toxins; D001974:Bromosuccinimide
Izmenenie biologicheskikh svoĭstv botulinicheskogo neĭrotoksina tipa A pri khimicheskoĭ modifikatsii ostatkov triptofana i tirozina v ego molekule.